Residual Injurious Symptoms and Its Association With Neurodegenerative Outcomes in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: A Retrospective, Longitudinal Follow-up Study.

Background: The risk of neurodegenerative disorders in idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with residual injurious symptoms (RIS) after symptomatic treatment with clonazepam and/or melatonin is unclear.

Objective: The objective of this study was to determine the rate and correlates of RIS and its association with the risk of neurodegenerative diseases in patients with iRBD.

Methods: This was a retrospective cohort study. RIS was defined by the RBD Questionnaire-Hong Kong (RBDQ-HK) as the presence of residual sleep-related injuries or potential injurious behaviors for at least once a month after at least 1 year of treatment.

Results: A total of 15 out of 133 (11.3%) patients with iRBD (age at diagnosis = 66.5 ± 7.3 years, 77.4% male) had RIS after 2.7 years of treatment. Patients with RIS were younger at both onset and polysomnography-confirmed diagnosis of iRBD (years, mean ± standard deviation, 56.3 ± 6.9 vs. 61.8 ± 7.6, P = 0.01; 61.2 ± 4.2 vs. 67.2 ± 7.4, P < 0.001, respectively), had more severe behavioral symptoms at diagnosis (both RBDQ-HK total score and behavioral subscore, P = 0.01), and used a higher maximum dose of clonazepam (mg; median [interquartile range], 1.5 [1.0] vs. 1.0 [1.0], P = 0.01). RIS was probably associated with a higher risk of developing dementia with Lewy bodies (adjusted hazard ratio [95% confidence interval], 5.47 [1.71-17.46], adjusted for onset age of RBD), but not Parkinsons's disease in the follow-up.

Conclusion: RIS is not uncommon in patients with iRBD despite long-term medication treatment. An earlier onset and more severe clinical profile are associated with RIS. The prediction of RIS toward dementia with Lewy bodies but not PD suggests that RIS may probably help to identify the specific risk of different subtypes of α-synucleinopathy. © 2020 International Parkinson and Movement Disorder Society.